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United States Patent |
5,505,088
|
Chandraratna
,   et al.
|
April 9, 1996
|
Ultrasound microscope for imaging living tissues
Abstract
A series of devices for in vivo imaging of cellular architecture in a
variety of tissues. A 200 MHz transducer is mounted on the tip of a
cardiac catheter, gastroscope, colonoscope, bronchoscope, laparoscope or
similar device, where it is moved mechanically to produce B-mode images of
cells in the tissue. The ultrasound beam is focused in a subsurface region
of tissue, and ultrasound which is backscattered from the focal zone is
analyzed to produce images. Because heart motion may interfere with
cardiac imaging, images are gated in mid-diastole for cardiac
applications.
Inventors:
|
Chandraratna; P. Anthony N. (Rancho Palos Verdes, CA);
Stern; Roger A. (Cupertino, CA)
|
Assignee:
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Stellartech Research Corp. (Mountain View, CA)
|
Appl. No.:
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102613 |
Filed:
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August 27, 1993 |
Current U.S. Class: |
73/623; 600/461; 600/466 |
Intern'l Class: |
G01N 029/04; A61B 005/04 |
Field of Search: |
128/662.06,662.03,662.05
73/606,618,623
|
References Cited
U.S. Patent Documents
4546771 | Oct., 1985 | Eggleton et al. | 128/660.
|
4862893 | Sep., 1989 | Martinelli | 128/662.
|
4869258 | Sep., 1989 | Hetz | 128/660.
|
4886059 | Dec., 1989 | Weber | 128/662.
|
4917097 | Apr., 1990 | Proudian et al. | 128/662.
|
4930515 | Jun., 1990 | Terwilliger | 128/662.
|
4967752 | Nov., 1990 | Blumenthal et al. | 128/660.
|
5158088 | Oct., 1992 | Nelson et al. | 128/662.
|
5354220 | Oct., 1994 | Ganguly et al. | 128/662.
|
5372138 | Dec., 1994 | Crowley et al. | 128/662.
|
5373845 | Dec., 1994 | Gardineer et al. | 128/662.
|
Primary Examiner: Chilcot; Richard
Assistant Examiner: Noori; Max H.
Attorney, Agent or Firm: Hite; Eppa
Claims
We claim:
1. Ultrasound microscope means comprising:
delivery means having a body with inside and outside surfaces, a distal
tip, and a lengthwise axis;
pivot means, secured to said tip, for mounting a transducer means pivotally
around a pivot axis normal to said lengthwise axis;
ultrasound transducer means, mounted on said pivot means and positionable
on a surface of in-vivo tissue to be imaged, for transmitting and
receiving ultrasound containing frequency components in a bandwidth
centered at approximately 200 MHz in beams to create A-scan lines forming
an imaging surface which includes said lengthwise axis; and
actuator means disposed at a first position for reciprocating said
transducer means to scan ultrasound beams at angles to create a B-scan
sector lying on said imaging surface;
conductor means for providing electrical signal connections to said
transducer means and to said actuator means, disposed inside said delivery
means; and
controller means for controlling electrical signals flowing through
respective conductor means to said transducer means and to said actuator
means.
2. Ultrasound microscope means as recited in claim 1 and comprising:
acoustically transparent window means disposed on said distal tip, and
coupling medium means for transmitting ultrasound between said transducer
means and said window means.
3. Ultrasound microscope means as in claim 2 wherein said pivot means
comprises a peripheral hinge.
4. Ultrasound microscope means as in claim 3 wherein said conductor means
for said transducer comprises coaxial cable.
5. Ultrasound microscope means as in claim 4 wherein said transducer
assembly comprises a polyvinylidene fluoride transducer and film
metallizations on both sides of said transducer, and a backing and support
means.
6. Ultrasound microscope means as recited in claim 2 wherein said pivot
means comprises a ball joint disposed on said lengthwise axis.
7. Ultrasound microscope means as recited in claim 6 wherein said conductor
means for said transducer means comprises a twisted pair.
8. Ultrasound microscope means as recited in claim 6 and further comprising
a second actuator means disposed at a second position to scan sectors at
any angle.
9. Ultrasound microscope means as recited in claim 1 wherein said actuator
means comprises a piezoelectric bimorph,
10. Ultrasound microscope means as recited in claim 2 and further
comprising an inflatable balloon disposed around said distal tip for
positioning of said tip in a depression of an irregular surface of in-vivo
tissue, and for preventing penetration of said tip into the surface of
said in-vivo tissue to be imaged.
11. Ultrasound microscope means as recited in claim 10 wherein said balloon
protrudes beyond said distal tip and forms a seal to trap body fluids
between said surface and said tip.
12. Ultrasound microscope means as recited in claim 10 wherein said balloon
recedes inside said distal tip.
13. Ultrasound microscope means as recited in claim 1 comprising controller
means including:
a control signal generator for supplying control signals to said actuator
means;
transmitter means for generating electrical energy;
electrical conductor means for conducting control signals to and from said
transducer and actuator means;
receiver means for amplifying electrical signals generated by backscattered
ultrasound energy received through said transducer means;
switch means for connecting said transducer means to said transmitter means
during transmission or alternately to said receiver means during
reception;
pixel-data storage means;
pixel data converter means to convert pixel data to output display data;
display means responsive to display data; and
coordination means for synchronizing said transmitter means, actuator
means, switch means, receiver means, pixel data storage and converter
means, and display means.
14. Ultrasound microscope means as in claim 1 wherein said frequency
components are within a bandwidth of approximately 200 MHz.
15. Ultrasound microscope means as in claim 14 wherein said frequency
components are within a bandwidth of approximately 100 MHz.
Description
BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates generally to ultrasound visualization
techniques and more particularly to catheter or endoscope based ultrasound
microscopes.
2. Prior Art
Conventional catheters have been designed with ultrasound transducers
operating at between 5 and 30 MHz which are introduced inside the bodies
of patients. These low frequencies of ultrasound can create images to
depths of several centimeters inside tissues. For a given transducer
diameter, the axial resolution of an ultrasound beam increases as the
frequency increases. The beam resolution along its axis is increased when
pulse duration is decreased, by transmitting a pulse with increased
bandwidth. Transducer diameter, frequency, bandwidth and sensitivity must
be optimized simultaneously when designing ultrasound transducers.
Conventionally, 2.25 or 3.0 MHz transducers are used to image cardiac
structures such as the mitral, tricuspid and aortic valves and left
ventricular walls. Transducers operating at 5 MHz placed on infants and
childrens bodies provide better resolution, although the beam penetration
depth is less than with lower frequencies. Transducers operating at 5 or
7.5 MHz can image superficial structures such as the carotid and femoral
arteries. Transesophageal echocardiography utilizes 5 or 7.5 MHz
transducers with considerably improved image quality due to the higher
frequencies and shorter distances from the transducer to the heart. Higher
20 to 30 MHz frequency transducers have been mounted on the tips of
cardiac catheters for intravascular imaging, and have provided excellent
resolution of the intima, media and adventitia of arterial walls.
Transducers operating at 2 to 30 MHz frequencies provide excellent images
of the heart and other organs, but still cannot image cellular detail.
When transducer frequency is increased to 1000 MHz, the ultrasound
wavelength is significantly decreased and approaches that of light. The
image resolution achievable with ultrasound at 1000 MHz is approximately 1
to 1.5 microns, which enables imaging cellular detail. Transducers
operating at 600 to 1000 MHz can accurately assess myocardial cellular
detail.
Prior art has imaged cellular characteristics in thin (5 micron) sections
of tissue. Myocardial pathology, which is characterized by myocyte
necrosis, lymphocytic infiltration and interstitial fibrosis, can be
visualized clearly with very high frequency ultrasound. However,
ultrasound in the very high frequency range trades off the disadvantage of
very shallow penetration into tissue.
U.S. Pat. No. 4,546,771 by Eggleton et al. discloses a biopsy needle for
positioning an ultrasound transducer capable of producing and receiving
high (100 to 500 MHz) frequency ultrasound. Passing the needle into
tissues enables microscopic examination of tissues within living bodies.
Inside the needle a transducer generates an ultrasonic beam which is
directed axially, then reflected off a mirror located at 45.degree. in the
needle to be directed radially from the needle and focused at a point in
the tissue. The tissue backscatters ultrasound toward the needle, where
the 45.degree. mirror reflects it up along the needle axis to be received
by the transducer. A piezoelectric bimorph actuator can reciprocate the
mirror along the needle axis to produce a sequence of parallel A-scans,
for forming a B-scan in a plane parallel to the needle axis. A second
embodiment utilizing a rotary actuator can oscillate the mirror around the
needle axis. This produces a sequence of radial A-scans for forming a
B-scan in a plane perpendicular to the needle axis. Eggleton emphasizes
frequencies between 400 and 500 MHz.
In the inventors experience, 400 MHz or higher frequency transducers are
not satisfactory for imaging cells in thicksample sections of tissue. This
is due to the extremely shallow depth of penetration of ultrasound at such
high frequencies. In-vivo ultrasonic imaging of details of cells from
thick sections is not known to have been reported.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an ultrasound
microscope means for imaging living tissues with resolution sufficient to
visualize individual cells.
It is another object to visualize individual cells in-vivo using minimally
invasive means.
It is a further object to provide ultrasound microscope means for imaging
forward from the tip of a catheter.
It is an additional object to provide ultrasonic microscopes incorporated
into various devices such as cardiac catheters, hysterocopes,
colonoscopes, gastroscopes, bronchoscopes, laparoscopes or in surface
imaging devices.
The present invention is an ultrasonic microscope which operates at a
frequency substantially above those of conventional ultrasound imaging
devices and substantially below those of conventional ultrasound
microscopes, preferably around 200 MHz. The microscope comprises catheter
means having a body with inside and outside surfaces ending with a distal
tip, and a long axis. A pivot means mounts a transducer means around a
pivot axis normal to the long axis, onto the inside surface adjacent to
the tip of the catheter. An ultrasound transducer assembly is positioned
pivotally on the pivot means. The transducer transmits and receives high
frequency ultrasound in beams for A-scan lines in a plane which includes
the long axis. An actuator reciprocates the transducer to scan the
ultrasound beams at increasing angles along an arc across a B-scan sector
in the plane. Conductors provide ultrasound energy for the transducer and
power for the actuator which are disposed inside the catheter. A
controller controls the electrical energy flowing through respective
conductors to the transducer and to the actuator.
Among the advantages of the invention are that scanning forward from a
catheter enables a transducer to look ahead to and to approach, at an
angle to surfaces to be imaged. Another advantage is that it allows
imaging without penetrating the tissues.
These and other features of the invention will become more apparent through
reference to the accompanying Detailed Description and Drawing.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a cross-section along the long axis through a catheter tube, its
distal tip, an ultrasound transducer and an actuator, and shows a sequence
of radial A-scan lines forming a B-scan sector, according to the
invention;
FIG. 2 shows the invention in a first embodiment with its pivot means as a
peripheral hinge;
FIG. 3 is a cross-section through a second embodiment with its pivot means
as a central ball joint;
FIG. 4 is a cross-section through a third embodiment wherein the transducer
means protrudes outside an inflatable balloon;
FIG. 5 is a cross-section through a fourth embodiment like FIG. 4 except
the transducer means is recessed inside an inflatable balloon; and
FIG. 6 is a schematic block diagram of a controller system for transmitting
and receiving signals for an ultrasound microscope according to the
invention.
DETAILED DESCRIPTION OF THE INVENTION
For potential in vivo applications, lower frequency ultrasound transducers
can provide deeper penetration in tissue, but ultrasonic microscopy
development has lacked a demonstration that lower frequency transducers
could reliably detect cellular abnormalities. The present invention
establishes minimum frequencies necessary for cellular imaging.
Cardiac cell detail, including normal cardiac myocytes and pathological
phenomenon such as interstitial fibrosis, cell fallout and round cell
infiltration, can be clearly identified in thin (5 .mu.m) sections of
tissue by using 1000, 600, 400 or 200 MHz transducers. However,
backscatter images of cells within thick sections cannot be obtained using
600 or 400 MHz transducers due to their inadequate tissue penetration and
the weakness of backscattered signals. At the lower end of the range of
potential usable frequencies, with 100 MHz transducers having inadequate
resolution cellular imaging is not practical.
The invention teaches the feasibility of using a 200 MHz transducer for
backscatter imaging of cells from full thickness subsurface layers of
myocardium. After ultrasonic imaging experiments, myocardial tissue was
sectioned in 5 micron thick sections parallel to the imaging plane,
stained with hematoxylin and eosin, and then examined by light microscopy.
The diameters of cells measured by high frequency ultrasound were similar
to those of cells measured by light microscopy. The ultrasound images of
cardiac myocytes were comparable to the light microscope images.
Referring to FIG. 1, in the present invention an ultrasonic microscope 10
comprises a catheter-type delivery means 18 with a distal tip 16, and
generic pivot means 20 for mounting ultrasound transducer 12 to be scanned
with a mechanical linear actuator 14. Transducer and actuator control
signals are supplied through electrical conductors 21 and 24 within the
catheter tube 26. Transducer 12 transmits an ultrasonic beam through an
acoustic lens 28 having a concave surface 30 which focuses the ultrasound
to a focal point in the tissue. Alternatively, transducer surface 30 can
be concave to focus the ultrasound. Pointing transducer 12 determines the
direction of the beam. Where transducer 12 points along axis A through tip
16, it focuses at the nominal focal point (NFP). The focal point is
deflected from the NFP as the transducer direction is changed.
The ultrasound beam has a Near Field depth NF=d.sup.2 /.lambda. where d (=2
mm) is the transducer 12 diameter and .lambda.=c/f (.congruent.7.mu.m @200
MHz) is the ultrasound wavelength.
Transducer 12 having diameter d=2 mm and frequency f=200 MHz projects
transmit beam T which is collimated through possibly 10 cm of depth. This
is farther than the nominal focal point depth, which is constrained by the
penetration of ultrasound at 200 MHz. An appropriate lens 28 or surface 30
curvature focuses the beam for maximum resolution focal spot size. The
focal spot pixel diameter can be as narrow as 7 .mu.m. Its resolution is a
diffraction limited function of transducer diameter d (preferably 2 mm),
focal length FL (preferably 3 mm) and frequency f (preferably 200 MHz).
The pixel length or axial depth resolution varies directly with the
bandwidth (inversely with the pulse duration of ultrasound). It is
.congruent.7 .mu.m for a bandwidth of 200 MHz. Shorter pulses require
higher bandwidths.
In microscope operation, an ultrasonic pulse centered at a frequency of
preferably .congruent.200 MHz is transmitted into the tissue (not shown)
around the tip. The ultrasonic signal's resulting backscatter is next
received, amplified and envelope-detected, to form individual A-scan
lines. The ultrasound beam is mechanically scanned orthogonally to its
axis, which moves across a B-scan sector through an arc around a pivot
axis. The pivot axis is perpendicular to but does not necessarily
intersect the long axis A of the catheter 18. A-scan lines radially at
incremental angles together form a B-scan. For example, two hundred
A-scans spaced angularly at 0.05 degrees together form a sector
10.0.degree. wide. At an NFP of 2.0 mm, the separation between A-line
pixels is 1.7 microns. The time to receive backscatter signals from each
A-line is under 5 microseconds. A thirty frame-per-second rate allows 166
microseconds per radial A-scan, which is substantially greater than the
time required to acquire data from an individual A-scan line.
FIG. 2 shows the invention in a first embodiment having an outer catheter
body 26 containing coaxial cable connections 22 for electrical signals to
transducer 12, and containing drive conductors 24 for energizing a
scanning-actuator means 14 such as a piezo-bimorph. Outer catheter body 26
terminating tip 16 contains ultrasound transducer 12 and coupling fluid 32
for transmitting ultrasonic energy to the end of catheter 18. Catheter tip
16 has acoustic window 34 which passes ultrasound into the tissue, and
admits energy backscattered from the tissue, as data to be received by
transducer means 12.
Transducer 12 is mounted on a pivot means or rotational joint in the form
of a peripheral hinge 42 which allows scanning actuator means 14 to move
transducer 12 for performing a B-mode scan.
Transducer 12 as shown in FIG. 2 is fabricated by a backing material 46
attached to the end of coaxial cable 22, and curved to focus ultrasonic
energy at a desired point inside tissue. A piezoelectric film 48 of for
example polyvinylidene fluoride PVDF on both sides has applied
metallization 50 which conforms to shaped backing material 46.
Alternatively, a transducer 12 could be embodied using zinc oxide, lithium
niobate or PZT, on a lens of sapphire or quartz. The coaxial cable 22
center conductor 51 pierces backing material 46 and forms an electrical
contact with back metallization 50 on piezoelectric film 48. The coaxial
cable 22 outer shield conductor 52 extends over shaped backing material 46
and forms an electrical contact with front metallization 50.
A linear actuator 14 is attached to one outer edge of the transducer
assembly 12, and is in turn secured to the inside of catheter body 26. A
rotational joint 42 pivot means is attached to the opposite edge of
transducer assembly 12. When the attached electrical drive conductors 24
energize actuator 14, this rotates transducer assembly 12 to perform a
B-scan. The FIG. 3 embodiment has the advantage of integrating the coaxial
cable 22 and the transducer assembly 12, and minimizes potential
electrical impedance mismatch.
FIG. 3 shows the invention in an alternate embodiment which has outer
catheter body 26 containing wires as twisted pair 23 connections for
electrical signals to transducer 12. Body 26 also contains drive
conductors 24 for powering scanning actuator means 14. The outer catheter
body 26 terminating tip 16 contains ultrasound transducer 12 and coupling
fluid 32 to transmit ultrasonic energy to the end of the catheter. The
catheter tip 16 contains acoustic window 34 which transmits ultrasound
into the tissue, and receives energy backscattered from the tissue.
Transducer 12 is mounted on a centrally located rotational or ball type
joint 43 allowing scanning means 14 to move the transducer 12 to perform a
B-mode scan.
Transducer 12 as shown in FIG. 3 is embodied by a backing material 46
curved to focus ultrasonic energy. A piezoelectric film 48 of for example
PVDF has applied metallization 50 on both sides conforming to shaped
backing material 46. One of the signal conductor wires of twisted pair 23
electrically contacts back metallization 50 of piezoelectric film 48. The
other wire of pair 23 electrically contacts front metallization 50.
A linear actuator 14 is attached to an edge on the outside of transducer
assembly 12 and is in turn secured to the inside of catheter body 26.
Pivot means in the form of a rotational joint 43 is centered at the back
of backing material 46. When electrical drive conductors 24 energize
actuator 14 this rotates transducer assembly 12 to perform a B-scan.
A central rotational joint 43 in the form of a ball joint allows two
degrees of rotational freedom. Then, a second linear actuator (not shown)
can be located 90.degree. around the rim from first actuator 14. This
allows selecting B-scan sector plane orientations at any desired angle
around long axis A of catheter 18. B-scans taken at multiple angles allow
scanning conical volumes diverging out axis A. Such image-scan data can be
time-filtered to form C-scan slices in any plane within the conical
volume. Other processes, including 3D displays, can be practiced on such
image scan data.
FIG. 4 shows the invention in a third embodiment in which catheter tip 16
protrudes 1/2 mm beyond the outside surface of an inflatable surrounding
balloon 54. This geometry assists in imaging a myocardial surface 56 and
in preventing penetration of such surfaces.
FIG. 5 shows a fourth embodiment with catheter tip 16 recessed 1/2 mm
inside the surface of an inflated surrounding balloon 55. This recess
dimple 58 traps blood to provide a coupling interface to wall 59.
FIG. 6 shows an electronic controller system 60 preferred for operating an
ultrasonic microscope 10 of the present invention. A transmit signal
generator 62 creates either an impulsive or short sinusoidal electrical
pulse of a voltage suitable to drive piezoelectric transducer 12 for
transmitting ultrasonic energy into surrounding tissue. During
transmission, transmitter 62 is connected through a transmit/receive (T/R)
switch 64 to the signal connection 21 of transducer 12, which is located
inside catheter tube 18. Electricity drives piezoelectric transducer 12 to
transmit ultrasonic energy into the tissue. The ultrasonic pulse
transmission is immediately followed as the T/R switch 64 is placed into
receive mode. Ultrasonic energy backscattered and impinging on transducer
12 is converted into electrical energy, passed through the T/R switch and
applied to a receiver 66. Receiver 66 amplifies, filters, time gain
compensates optionally to correct tissue attenuation effects, and envelope
detects to generate signals representative of tissue backscattering.
The receiver 66 signal output is input to a scan converter 68. Then Input
data is taken at arbitrary scanning geometries and generates an image for
storage in a scan converter memory (not shown). The scan converter memory
is read out for display for example on a standard raster scan CRT 70. Scan
converter 68 and linear actuator drive means 72 are time-coordinated so
that received data is stored in the proper scan converter 68 memory
locations. Linear actuator drive means 72 generates electrical drive
signals for moving transducer 14 synchronously with storing data in the
scan converter memory. Overall system operation is controlled by system
control processor 74, which also accepts user commands from an input
device 76 such as a keyboard.
The present invention is described in terms of the preferred embodiments
which may be modified without departing from the spirit of the invention.
While the invention is presented as a cardiac catheter microscope, with
suitable modifications it could be adapted for use in a hysteroscope,
colonoscope, gastroscope, bronchoscope, laparoscope or surface imaging
ultrasonic microscope. It is intended that the following claims be
interpreted as having scopes covering modifications within the spirit of
the invention.
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